Test positivity for Maedi-Visna virus and Mycobacterium avium ssp. paratuberculosis in Sarda ewes: Effects on milk composition and coagulation traits and heritability estimates for susceptibility.

Maedi-Visna virus (MVV) and Mycobacterium avium ssp. paratuberculosis (MAP) are two pathogens that cause chronic, production-limiting diseases in dairy sheep. Although they are present worldwide, there are no detailed reports on their actual effects on milk traits in the literature. This study was designed to investigate the effects of test positivity to MVV and MAP on ovine milk yield, composition and coagulation properties, and curd-firming over time (CFt) variables in clinically healthy animals at the field level. The additive genetic variation and heritabilities of MVV and MAP positivity were also estimated. Milk samples were collected from 1,079 Sarda sheep kept on 23 farms, and pedigree information was obtained from the flock book. Milk yield was also recorded on the sampling date. Positivity for MVV and MAP was determined from milk samples using indirect ELISA test kits. Milk composition traits were measured by spectroscopy, milk coagulation properties were measured with a Formagraph (Foss Italia, Padua, Italy), and CFt traits were calculated using the data from the Formagraph diagram. The effects of MVV and MAP positivity on milk traits were determined through a set of mixed linear models, which took into account various sources of variation, such as days in milk, parity, and flock effects, and included the effects (positive or negative) of the 2 pathogens. A Bayesian threshold sire model with sire relationship was used to estimate genetic variation and heritability. The overall animal prevalence of MVV-positive ewes was 43.6%; on only 1 farm of the 23 tested were all sampled ewes negative. An overall animal prevalence of 10.6% was recorded for MAP, with 4 farms at 0%. Positivity for MVV significantly affected the logarithmic score of the bacterial count, curd firmness after 30 min and 45 min, and the curd-firming instant rate constant. We found significant effects of MAP infection on milk composition, pH, and rennet coagulation time. The mean of the posterior distributions of heritability estimates on the liability scale was 0.15 for MAP and 0.07 for MVV. Our results demonstrate that only a few traits are negatively affected by MVV and MAP positivity, and that there is exploitable genetic variation in MVV and MAP susceptibility in dairy sheep.

Natural cases of visna in sheep with myelitis as the sole lesion in the central nervous system.

Of 118 sheep with visna, 12 showed myelitis as the only nervous lesion. They were ovine lentivirus (OvLV)-seropositive and provirus DNA was demonstrated by LTR-PCR in all the samples with lesions. Clinically, all showed hindlimb paralysis and some were completely recumbent. Grossly, a swollen and discoloured area was identified in the white matter in 10 sheep. Microscopical changes consisted of a wedge-shaped area of non-suppurative leucomyelitis with mononuclear perivascular cuffing, demyelination and white matter degeneration. Except for two samples, grey matter was affected adjacent to severe white matter lesions. Three different microscopical patterns of lesion were identified, all having in common the presence of perivascular inflammation: the so-called vascular pattern was characterized by perivascular cuffs with minimal lesions in the adjacent neuroparenchyma; the malacic pattern, which was the commonest type, was characterized by severe white matter destruction and small numbers of macrophages; and the infiltrative pattern was characterized by a severe infiltrate of histiocytes in the parenchyma. Maedi-visna virus antigen was detected immunohistochemically only in areas with lesions, and the degree of immunolabelling was unrelated to the severity of the damage. Diagnosticians should bear in mind that a considerable number of visna cases show only spinal cord lesions. Examination of paraffin wax-embedded samples by LTR-PCR and immunohistochemistry would seem useful in confirming a histopathological diagnosis of visna from spinal cord samples.

Maedi-visna virus and its relationship to human immunodeficiency virus.

Maedi-visna is a slow virus infection of sheep leading to a progressing lymphoproliferative disease which is invariably fatal. It affects multiple organs, but primarily the lungs where it causes interstitial pneumonia (maedi). Infection of the central nervous system was commonly observed in Icelandic sheep (visna), infection of mammary glands (hard udder) in sheep in Europe and the USA, and infection of the joints in sheep in the USA. The name ovine progressive pneumonia (OPP) is commonly used in the USA and ovine lentivirus (OvLV) infection is also a name used for maedi-visna. A related infection of goats, caprine arthritis-encephalitis (CAE), is common in Europe and the USA. The natural transmission of maedi-visna is mostly by the respiratory route, but also to newborn lambs by colostrum and milk. Intrauterine transmission seems to be rare and venereal transmission is not well documented. Macrophages are the major target cells of maedi-visna virus (MVV), but viral replication is greatly restricted in the animal host, apparently due to a posttranscriptional block. The low-grade viral production in infected tissues can explain the slow course of the disease in sheep. The lesions in maedi-visna consist of infiltrates of lymphocytes, plasma cells, and macrophages, and are detectable shortly after experimental transmission. Several studies indicate that the lesions are immune mediated and that cytotoxic T-lymphocytes may be important effector cells. The persistence of the MVV infection is explained by a reservoir of latently infected blood and bone marrow monocytes, which migrate into the target organs and mature into macrophages with proviral DNA transcription, but limited replication of virus. The MVV particles are morphologically similar to those of other retroviruses and the mode of replication follows the same general pattern. The genome organization and gene regulation resembles that of other lentiviruses. In addition to gag, pol and env, MVV has three auxiliary genes (tat, rev and vif), which seem to have similar functions as in other lentiviruses, with a possible exception of the tat gene. A determination of the 9200 nucleotide sequence of the MVV genome shows a close relationship to CAE virus, but limited sequence homology with other lentiviruses, and only in certain conserved domains of the reverse transcriptase and possibly in the surface protein. MVV infection in sheep and HIV-1 infection in humans have a number of features in common such as a long preclinical period following transmission, and a slow development of multiorgan disease with fatal outcome. A brief early acute phase, which is terminated by the immune response, is also an interesting common feature. Like HIV-1, MVV is macrophage tropic and the early stages of the HIV-1 infection which affect the central nervous system and the lungs are in many ways comparable to maedi-visna. In contrast to HIV-1, MVV does not infect T-lymphocytes and does not cause T-cell depletion and immunodeficiency. This is responsible for the difference in the late stages of the HIV-1 and MVV infections and the final clinical outcome. Despite limited sequence homology, certain proteins of MVV and HIV-1 show structural and functional similarities. Studies of MVV may therefore help in the search for new drugs against lentiviruses, including HIV-1.

[Clinical findings and diagnostic procedure in a dairy sheep with visna]. / Klinische Befunde und diagnostisches Vorgehen bei einem Milchschaf mit Visna.

The goal of this report was to describe the clinical signs and diagnosis of Visna in a seven-year-old East Friesian milk sheep. A striking feature was that the ewe's behaviour changed frequently. At one time, the ewe was somnolent. A few minutes later, the sheep was alert and eating hay. The ewe was thin. It had a slight head tilt and a severe generalised ataxia. Based on the neurological symptoms and chronic weight loss, a tentative diagnosis of visna was made. Serological testing for maedi-visna was positive, and the ewe was euthanised. A postmortem examination was performed, and lung and brain samples were collected aseptically. Cell cultures from these organs were positive for viral enzymatic reverse transcriptase and for maedi-visna RNA.

Visna-maedi virus induces interleukin-8 in sheep alveolar macrophages through a tyrosine-kinase signaling pathway.

The mechanisms leading to the severe lung damage seen in some sheep naturally infected with the visna-maedi virus, and to pulmonary lesions in other lentiviral diseases, appear to involve the recruitment of large numbers of uninfected inflammatory cells. Only a few alveolar macrophages from experimentally infected lambs express virus, but high levels of interleukin (IL)-8 mRNA are present in the macrophage population. In vitro infection with visna-maedi virus at low multiplicity of alveolar macrophages from uninfected sheep also strongly induced the expression of IL-8 mRNA and the accumulation of IL-8 in the extracellular medium. An initial peak of IL-8 mRNA expression at 3 or 6 h after infection was followed by a fall, then a more persistent expression lasting at least 48 h after infection. The early peak was accompanied by expression of mRNA for IL-1beta, and a possible rise in tumor necrosis factor alpha (TNFalpha) mRNA, although this was frequently elevated in uninfected ovine alveolar macrophages. Interestingly, these events occurred identically in cells treated with non-infectious heat-treated virus, suggesting that interaction between viral components and cellular membrane receptors could suffice for both early and late IL-8 induction. The level of IL-8 mRNA induced by treatment with live or inactivated virus could be severely reduced by pretreatment of the macrophages with genistein but not with staurosporine, suggesting the involvement of a tyrosine-kinase signaling pathway. The early induction of IL-1beta and possibly of TNFalpha may explain the occurrence of a later persistent expression of IL-8 mRNA through an autocrine mechanism.

Maedi-Visna and ovine progressive pneumonia.

Maedi-Visna and ovine progressive pneumonia are disease of sheep that are caused by ovine lentivirus and characterized by chronic inflammation of the lungs, mammary glands, joints, and central nervous system. Although tremendous progress in research has led to a better understanding of the pathogenesis of these diseases, many questions still remain. Much of the mystery is the result of the complexity of the ovine lentivirus genome and the intricate interactions of the virus with the host during replication. Discoveries in molecular virology are shedding light on these interactions and novel approaches to prevent and control lentivirus infections are being explored. There is hope that some of these approaches will eventually be used to eradicate these diseases.

Clinicopathological investigation of primary, uncomplicated maedi-visna virus infection.

Maedi-visna virus infection in a flock of sheep in Scotland was associated with respiratory disease, neurological disease, mastitis and lameness. The major clinical signs were dyspnoea (particularly on exercise), progressive fore- and hindlimb ataxia and balance defects, mammary induration and multilimb lameness, occasionally with enlarged carpal joints. Pathological examinations revealed lesions in the lungs, central nervous system, mammary glands and joints which were consistent with those induced by maedi-visna virus. The was no clinical or pathological evidence of concurrent sheep pulmonary adenomatosis, and pulmonary bacterial infections, when they occurred, were superimposed on the lesions due to maedi-visna virus.